A review of combination therapy in patients with

benign prostatic hyperplasia

Trials of monotherapy with alpha(1)-adrenergic-receptor antagonists (alpha(1)ARAs) and 5

alpha-reductase inhibitors (5ARIs) have found that the former drug class is effective in managing
benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS) and improving
the maximal urinary flow rate in shortand long-term treatment, regardless of prostate size,
whereas the latter drug class is effective in reducing prostate size and preventing disease
progression in longer-term treatment. The differing mechanisms of action and areas of efficacy
of these 2 drug classes make them promising candidates for combination therapy.

OBJECTIVE:

This article reviews key trials of monotherapy and combination alpha(1)ARV5ARI therapy in the
treatment and prevention of BPH-related voiding dysfunction.

METHODS:

MEDLINE (1976-2006) and the Cochrane Central Register of Controlled Trials (1976-2006) were
searched for relevant clinical trials and reviews using the terms benign prostatic byperplasia,
lower urinary tract symptoms, LUTS, alpha-adrenergic-receptor antagonists, alpha-blockers, 5
alpha-reductase inhibitors, combination therapy, MTOPS, SMART, PREDICT, adverse events,
alfuzosin, doxazosin, tamsulosin, terazosin, dutasteride, and finasteride. Abstracts from selected
professional conferences also were reviewed.

RESULTS:

Three previous trials of alpha(1)ARA/5ARI therapy found no therapeutic benefit for combination
therapy relative to monotherapy, but their conclusions were limited to some extent by their
designs, particularly the duration of treatment. Data from the Medical Therapy of Prostatic
Symptoms (MTOPS) study, however, indicated a potential role for long-term use of
alpha(1)ARA/5ARI therapy, particularly in patients with greater symptom severity (mean score
of 17 on the American Urological Association symptom index), larger prostate volume (mean,
32 g), and higher prostate-specific antigen (PSA) levels (>1.5 ng/mL) at baseline. In the MTOPS
study, combination therapy with the alpha(1)ARA doxazosin and the SARI finasteride was
significantly more effective than either component alone in reducing BPH-related symptoms
(P=0.006 vs doxazosin monotherapy; P<0.001 vs finasteride monotherapy) and lowering the rate
of overall clinical progression (P<0.001 vs either monotherapy). In addition, there are data from
a subgroup analysis of MTOPS suggesting that the presence of prostatic inflammation may
indicate a greater likelihood of treatment efficacy with combination alpha(1)ARA/5ARI therapy.

CONCLUSIONS:

The available data suggest that combination alpha(1)ARA/5ARI therapy is beneficial in the
treatment of BPH and the associated symptoms. The greatest efficacy was evident in patients
with an enlarged prostate, more severe symptoms, and higher PSA levels. There are limited data
suggesting that the presence of prostatic inflammation may indicate a greater likelihood of
treatment efficacy with combination therapy.